[Dependence of the carcinogenic effect of N-nitrosomethylurea on its dosage and the age of female rats].

Female rats aged 3 and 15 months received single intravenous injections of 10, 20 or 50 mg/kg of N-nitrosomethylurea (NMU). The rate of 14-month survival (duration of experiment) in younger animals was 90, 61 and 42%, respectively, while in the older age group it was 15, 0 and 0%. In 3-month-old rats, a direct correlation was established between NMU dosage, on the one hand, and overall incidence of tumors as well as that of breast adenocarcinoma, renal, ovarian and colonic neoplasms, on the other. No dose-incidence correlation was found for any tumor site in 15-month-old animals. The incidence of NMU-induced uterine and cervical neoplasia was higher in the older age group while mammary, intestinal, ovarian and renal tumors were more frequent in younger rats. The results were evaluated versus the data on DNA alkylation, O6-methylguanine repair and DNA synthesis obtained from the same model. A key-role of age-related changes of proliferative activity of target tissues in the modifying effect of aging on NMU-induced carcinogenesis in rats was suggested.